The present investigation is designed to evaluate, in a longitudinal and cross-sectional study, the relative contributions of genetic, in utero and nutritional factors to the pathogenesis of childhood obesity. Oral glucose tolerance tests with measurement of serum insulin (or C. peptide) and plasma glucagon are performed in gestational and insulin-requiring diabetics during each trimester of pregnancy. At the same time, adipose tissue cell size is determined on needle aspirates of fat tissue. Diabetic control is assayed via monthly hemoglobin AlC, triglyceride, cholesterol and plasma amino acid measurements. Attempts at normalizing maternal blood glucose concentrations consist of dietary manipulation, multiple daily insulin injections, when indicated and specifically insulin treatment of 50% of the gestational mothers. Infants born to these mothers are followed with serial adipose tissue cellularity and metabolic studies and oral glucose tolerance tests. Growth is monitored with bone age determinations and careful measurements of height, weight, head circumference and skinfold thickness. In vivo and in vitro insulin sensitivity is investigated with serial insulin tolerance tests performed with gradually increasing insulin doses between .05 to .15 units per kilogram of body weight, adipocyte responses to insulin, and red cell insulin receptor studies. In addition, these studies are being compared with previous ones on a group of similar children now aged 8 years and followed since birth. Finally, parallel longitudinal studies are being performed in monozygotic and dizygotic twins ages 1 day through 14 years to further elucidate genetic factors in human obesity.